Asymmetric Propargylic Radical Cyanation Enabled By Dual Organophotoredox And Copper Catalysis

Alkynyl functional groups widely exist in many drugs and natural products,and can be converted into many other functional groups.Therefore,the synthesis and transformation of alkynes are of great significance.Catalytic asymmetric propargylation is an important reaction for the synthesis of alkynes with chiral centers,which has the characteristics of mild reaction conditions and good enantioselectivity.However,due to the strong coordination ability of cyano anion,this kind of reaction can not be used for catalytic asymmetric propargylic cyanogenation.So chemists need to develop new strategies and catalytic systems to solve this challenging question.In this thesis,propargylic alcohol was converted into 3,5-bis(trifluoromethyl)benzoyl ester with redox activity,and propargylic radical was produced by breaking C-O bond under visible light catalysis.At the same time,TMSCN was used as the source of cyano to slowly release the negative cyano ions and participate in the copper catalyzed asymmetric reaction,which realized the asymmetric propargylic cyanation.After screening,we determined the optimal conditions of the reaction:Ph-PTZ as photocatalyst,Cu(MeCN)4BF4 as copper source,indene substituted dioxazolin as chiral ligand,THF as solvent,after irradiating with 3W x 2 violet lamp for 24 hours,a series of propargylic nitriles were obtained in 57-97%yields and 83-98%ee.In this reaction,the substrates derived from phenylacetylene,alkylalkyne and enyne are all suitable for this reaction.In addition,we verified the photocatalysis mechanism by fluorescence quenching experiment,switching lamp experiment and quantum yield experiment,and explained the reaction path and stereo control model by nonlinear effect experiment and DFT calculation:The structure of all substrates and propargylic nitriles were confirmed by 1H NMR,13C NMR and HRMS,and the absolute configuration was determined by X-ray single crystal diffraction.